Biological sample analysis device

Abstract

To provide a user-friendly biological sample analysis device which can timely and simply wash an inner surface of a flow channel.SOLUTION: A biological sample analysis device includes: a dilution tank 1 for diluting a biological sample; a discharge nozzle 2 for injecting the biological sample or a washing liquid to the dilution tank 1; a flow-through type sensor 8 for analyzing the biological sample after dilution; and a waste liquid part 19 for disposing of a liquid after used in the analysis. A bypass line 13 for the washing liquid branched from the dilution tank 1 is connected to the waste liquid part 19 positioned on a downstream of the sensor 8 via a three-way electromagnetic valve 10 for switching the washing bypass line. The bypass line 13 for the washing liquid is a flow channel for the washing liquid substituting for a washing block, is branched on an upstream of the sensor 8, is connected at a position on a downstream of the sensor 8 via the three-way electromagnetic valve 10 for switching the washing bypass line, and then bypasses the sensor 8.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to technology for an apparatus for analyzing biological samples, and in particular to technology for preventing a decrease in the quality of the analysis due to contamination originating from the biological sample that occurs when the apparatus is continuously used. [Background technology]

[0002] Conventionally, various types of devices for analyzing biological samples are known. Examples of biological samples include urine, serum, plasma, whole blood, cerebrospinal fluid, etc. Examples of analytical devices include electrolyte analyzers, sugar analyzers, etc.

[0003] When a biological sample analyzer is used continuously, dirt occurs on the liquid-contacting part of the device (hereinafter referred to as the "inner surface of the flow path"). In many cases, dirt originates from organic matter (e.g., protein) or inorganic matter contained in the biological sample. In the early stages, dirt is often simply the adhesion of these substances to the inner surface of the flow path. However, if left unattended, the dirt grows as microorganisms grow using the adhesion as a foothold, or the microorganisms release substances outside the bacterial body (see, for example, Non-Patent Document 1 below). After the passage of time, dirt can become slimy, gel-like, or crystalline, as shown in Figures 7 and 8. Figure 7 shows gel-like dirt that has occurred at the top of the dilution tank, and Figure 8 shows cotton-like dirt that has clogged the discharge nozzle.

[0004] The grown dirt has various adverse effects on the biological sample analyzer. If it occurs in the dilution section, it may lead to poor dilution ratio or clogging of the discharge nozzle. Furthermore, if dirt occurs on the inner surface of the flow path upstream of the sensor, washing off after the previous sample measurement may be insufficient (so-called carryover), which may reduce the measurement accuracy. Furthermore, if dirt that occurs on metal parts is left unattended, it may accelerate the corrosion of the metal parts (for example, see Non-Patent Document 1 below). Furthermore, the attached dirt itself may have an electric charge, which may cause electrical noise.

[0005] In order to prevent adverse effects caused by dirt on the inner surface of the flow path, it is essential to remove the dirt at appropriate times (hereinafter referred to as "cleaning"). However, the cleaning solution used to remove the dirt may also deteriorate the sensor.

[0006] Fig. 6 is an enlarged view of the periphery of a cleaning block used in the prior art. Conventionally, when cleaning, it was necessary to remove the sensor and replace it with cleaning block 30, and then fill the flow path with cleaning liquid. For convenience, in Fig. 6, the same components as those in the embodiment (Figs. 3 and 4) are denoted by the same reference numerals.

[0007] However, replacing the sensor and cleaning block is a very tedious task for users, and as a result, cleaning is often insufficient, so the introduction of a more user-friendly cleaning method was desired.

[0008] As a conventional technique, a method for cleaning a flow cell type analyzer has been proposed (see Patent Document 1 below). However, this method aims to improve the efficiency of the operation of washing away the previous sample so as not to affect the subsequent sample, thereby improving the processing speed, and is not related to cleaning the dirt derived from the biological sample described above. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Publication number 3-42365 [Non-patent literature]

[0010] [Non-Patent Document 1] "Biofilms and Their Industrial Applications", Hideyuki Kanematsu et al., Yoneda Publishing, 2015. Summary of the Invention [Problem to be solved by the invention]

[0011] In conventional biological component measuring devices, the sensor and washing block must be replaced when cleaning to prevent adverse effects caused by dirt on the inner surface of the flow path. However, replacing the sensor and washing block is a very troublesome task for the user, and there was a problem in that it was not a user-friendly cleaning method.

[0012] In view of the above problems, an object of the present invention is to provide a user-friendly biological sample analyzer that allows the inner surface of a flow path to be easily cleaned at any time. [Means for solving the problem]

[0013] In order to solve the above problems, the biological sample analyzer of the present invention is a biological sample analyzer having a dilution section for diluting a biological sample, an ejection nozzle for injecting the biological sample or a cleaning solution into the dilution section, a flow-through type sensor for analyzing the biological sample after dilution, and a waste liquid section for discarding the liquid after use in the analysis, characterized in that a bypass line for cleaning solution branching off from the dilution section is connected via a valve to the waste liquid section located downstream of the sensor.

[0014] According to the above configuration, when dirt occurs on the inner surface of the flow path of the biological sample analyzer, the user can perform cleaning at any time with simple operations without having to replace the sensor with a cleaning block.

[0015] The flow-through sensor for analyzing a biological sample is characterized in that it is a flow-through ion-selective electrode.

[0016] According to the above configuration, when dirt occurs on the inner surface of the flow path of the biological sample analyzer, the user can perform cleaning at any time with simple operations without having to replace the ion selective electrode with a cleaning block.

[0017] The cleaning apparatus further includes a control unit that controls each part of the apparatus including the valve, and the control unit controls the opening and closing of the valve at a specified date and time, thereby automatically carrying out the cleaning operation.

[0018] With this configuration, dirt on the inner surface of the flow path of the biological sample analyzer can be washed at the appropriate time without the user having to give an instruction for operation.

[0019] The control unit is also characterized in that it automatically executes a cleaning operation when an index related to the quality of measurement detected by the sensor deviates from a threshold value.

[0020] According to the above configuration, when an index related to the quality of the analysis deviates from a threshold value, cleaning can be performed at the appropriate time without the user having to give an instruction for an operation. Effect of the Invention

[0021] The present invention has the advantage of being able to prevent, in an easier manner than before, degradation of analytical quality caused by contamination originating from biological samples that occurs when a biological sample analyzer is used continuously. [Brief description of the drawings]

[0022] [Figure 1] FIG. 1 is a fluid system diagram of a biological sample analyzer according to a first embodiment of the present invention. [Diagram 2] FIG. 2 is an enlarged view of the periphery of the dilution tank of the biological sample analyzer according to the first embodiment of the present invention. [Diagram 3] FIG. 3 is an enlarged view of the periphery of the washing bypass line of the biological sample analyzer according to the first embodiment of the present invention (part 1). [Figure 4] FIG. 4 is an enlarged view of the washing bypass line and its surroundings of the biological sample analyzer according to the first embodiment of the present invention (part 2). [Diagram 5] FIG. 5 is a diagram showing an example of the configuration of the control unit of the biological sample analyzer according to the first embodiment of the present invention. [Figure 6] FIG. 6 is an enlarged view of the periphery of a cleaning block used in the prior art. [Figure 7] FIG. 7 shows gel-like stains that occurred in the upper part of the dilution tank. [Figure 8]FIG. 8 is a diagram showing a flocculent stain that has clogged a discharge nozzle. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] The following describes in detail an embodiment of the present invention, but the present invention is not limited thereto.

[0024] (Biological sample analyzer) The biological sample analyzer of the present invention has a dilution section for diluting the biological sample, an ejection nozzle for injecting the biological sample or a cleaning solution into the dilution section, a flow-through sensor for analyzing the diluted biological sample, and a waste liquid section for discarding the liquid after use in the analysis.

[0025] The dilution section is composed of a dilution tank, a stirrer, and a dilution liquid outlet. Depending on the measurement method, a standard liquid outlet may be added. The stirrer can be freely selected from a stirring blade, magnetic stirrer, etc., as long as it matches the purpose. Considering the efficiency of washing away the sample and ease of maintenance, it is preferable to use a small magnetic stirrer. The material of the dilution tank can be appropriately selected from metal, glass, resin, etc. Among these, it is preferable to use a transparent resin from the viewpoint of visibility and workability.

[0026] The discharge nozzle has the function of injecting the biological sample or the cleaning solution into the dilution tank. If the same discharge nozzle is used for both the biological sample and the cleaning solution, the inner surface of the discharge nozzle can also be cleaned.

[0027] Examples of flow-through type sensors include sodium ion selective electrodes, potassium ion selective electrodes, chlorine ion selective electrodes, calcium ion selective electrodes, magnesium ion selective electrodes, etc. These are used together with a reference electrode. Also, sugar analysis sensors, amino acid analysis sensors, etc. can be used. Note that multiple types of ion sensors may be used in combination at the same time. Furthermore, sensors for obtaining information other than the analysis of biological samples, such as temperature sensors and pressure sensors, may be added. Using such sensors in combination may contribute to the automation of washing operations.

[0028] The waste liquid section is a mechanism for discharging the liquid after it has been used in the analysis (hereinafter referred to as "waste liquid"). If necessary, it can be used in combination with a solenoid valve or a syringe pump. With this configuration, it is possible to control the flow direction of the waste liquid and to forcibly discharge it.

[0029] The present invention is characterized in that a flow path for a cleaning liquid branches off from the dilution tank of the dilution section. This flow path for the cleaning liquid is arranged in a bypass manner to circumvent the sensor, and is connected to a waste liquid section located downstream of the sensor via a valve (hereinafter, this flow path will be referred to as a "cleaning bypass line"). The branching of the cleaning liquid tube from the dilution tank may be made from a side wall surface (wall surface other than the bottom surface or the top surface) of the dilution tank, and may be made from the front surface of the device (see FIG. 3 described later) or from the back surface of the device (see FIG. 4).

[0030] The material of the cleaning bypass line need only be durable enough to withstand the components of the cleaning liquid, and can be freely selected from among Teflon (registered trademark), silicone, ceramic, stainless steel, corrosion-coated metal, etc.

[0031] The method of arranging the cleaning solution can be selected as appropriate according to need, such as placing it in the same cup as the sample and arranging it on the trajectory of the tip of the discharge nozzle, or setting a bottle of the cleaning solution. It may also be introduced to the specified location via a tube from a bottle or pouch set in another location of the device. It is also possible to use a cassette in which a single dose is individually packaged. If the cleaning component is solid, the cleaning component and liquid component may be mixed in the device and then used as the cleaning solution.

[0032] The cleaning components can be selected according to the nature of the dirt. It is possible to use alkaline hypochlorites such as sodium hypochlorite and potassium hypochlorite, hypochlorous acid, sodium hydroxide, potassium hydroxide, alkaline percarbonates such as sodium percarbonate and potassium percarbonate, surfactants, etc. In addition, it is also possible to mix two or more cleaning components as long as the components of the cleaning solution do not react with each other to generate harmful substances.

[0033] (Embodiment 1) An embodiment of the biological sample analyzer of the present invention will be described below.

[0034] (Device Configuration) 1 is a fluid system diagram of a biological sample analyzer according to embodiment 1 of the present invention. An electrolyte analyzer (manufactured by A&T Corporation) was used here as the biological sample analyzer.

[0035] At the most upstream of the flow path, there are arranged a dilution tank (dilution section) 1 for diluting the biological sample, a discharge nozzle 2 for injecting the biological sample or washing solution into the dilution section, a discharge port 3 for the dilution solution, and a discharge port 4 for the standard solution. The structure of the dilution tank 1 and its surroundings is as shown in Figure 2.

[0036] 2 is an enlarged view of the periphery of dilution tank 1 of the biological sample analyzer according to the first embodiment of the present invention. A flow path 5 leading downstream is provided at the bottom of dilution tank 1, which bends laterally before heading toward dilution tank outlet 7 (the flow path from the bottom of dilution tank 1 to dilution tank outlet 7 is referred to as the "diluted sample outlet flow path"). A branch point 6 is present midway along the flow path to dilution tank outlet 7.

[0037] As shown in Fig. 1, an inlet 14 of a washing bypass line 13 is connected to the branch point 6 via a connector. A magnetic stirrer is provided on the back wall of the dilution tank 1, and is used to stir and mix the biological sample and diluent when analyzing the biological sample.

[0038] A flow-through sensor 8 was placed downstream of the dilution tank outlet 7. A sodium ion selective electrode 8c, a potassium ion selective electrode 8b, and a chlorine ion selective electrode 8a were adopted as the flow-through sensor 8, and used together with a reference electrode 8r and a liquid earth electrode (omitted in FIG. 1) (all manufactured by A&T Corporation). These electrodes were connected from upstream in the order of the liquid earth electrode, the chlorine ion selective electrode 8a, the potassium ion selective electrode 8b, the sodium ion selective electrode 8c, and the reference electrode 8r to form a flow path.

[0039] The biological sample analyzer has a signal processing circuit 31 which processes signals input to these multiple electrodes during biological sample analysis, a differential amplifier circuit 32 which amplifies the signals from each electrode, and a signal input circuit 33 which inputs signals to each electrode. Although not shown, the electromotive forces of the liquid earth electrode, chlorine ion selective electrode 8a, potassium ion selective electrode 8b, and sodium ion selective electrode 8c are measured by a calculation circuit as potential differences with the potential of reference electrode 8r used as the system ground. A control unit 100, which will be described later, has the functions of, for example, the signal processing circuit 31 and the calculation circuit, and processes data during biological sample analysis.

[0040] A three-way solenoid valve was placed downstream of the reference electrode 8r (this solenoid valve will be referred to as the "three-way solenoid valve 10 for switching the cleaning bypass line"). One inlet 11 of the three-way solenoid valve 10 for switching the cleaning bypass line was connected to the outlet 9 of the flow-through sensor, and the other inlet 12 was connected to the outlet 15 of the cleaning bypass line 13. The outlet of the three-way solenoid valve 10 for switching the cleaning bypass line was connected to a waste liquid line 16 leading to a waste liquid section 19.

[0041] Figures 3 and 4 are enlarged views of the periphery of the washing bypass line of the biological sample analyzer according to the first embodiment of the present invention. In Figure 3, the washing bypass line 13 branches off from the front of the apparatus, and in Figure 4, the washing bypass line 13 branches off from the rear of the apparatus. The washing bypass line 13 branches off upstream of the flow-through sensor 8, is arranged in a bypass shape to detour around the flow-through sensor 8, is connected via a three-way solenoid valve 10 for switching the washing bypass line downstream of the flow-through sensor 8, and is connected to a waste liquid section 19.

[0042] The flow of liquid from the dilution tank 1 can be controlled by sending an electrical signal from the control unit to the three-way solenoid valve 10 for switching the washing bypass line. When analyzing a diluted biological sample, an instruction is given to send the biological sample dilution liquid in the dilution tank 1 to the waste liquid section 19 via the flow-through sensor 8. When washing is performed, an instruction is given to send the washing liquid in the dilution tank 1 to the waste liquid section 19 via the washing bypass line 13.

[0043] 5 is a diagram showing an example of the configuration of the control unit of the biological sample analyzer according to the first embodiment of the present invention. For example, control unit 100 comprises a CPU 101, ROM 102, RAM 103, a display 104, and a network I / F (interface) 105. Each of components 101 to 105 is connected to a bus 110.

[0044] The CPU 101 is responsible for overall control of the biological sample analyzer. The ROM 102 stores various data such as a boot program that starts up the biological sample analyzer, and programs that control measurement processes and each part such as solenoid valves and pumps. The RAM 103 is used as a work area for the CPU 101.

[0045] Display 104 displays various data. In the present invention, display 104 not only allows the user to recognize the status of the device, but also functions as a human interface for operating and inputting program settings. Network I / F 105 controls data communication between the biological sample analyzer and various external devices.

[0046] The control unit 100 shown in FIG. 5 performs a process for biological sample analysis based on the detection value of the flow-through sensor 8. In addition, the process for biological sample analysis can be switched to a process for cleaning at a predetermined time or other trigger. The process for cleaning described below is not limited to an automatic process performed by the control unit 100, but can also be a manual operation. Furthermore, the control unit 100 may manage the entire process while a part of the operation that requires visual confirmation or the like is manually operated by the user. In addition, as will be described later, the control unit 100 may start the process for cleaning when an index related to the quality of measurement detected by the flow-through sensor 8 due to the execution of the biological sample analysis deviates from a threshold value as a trigger for cleaning.

[0047] (Explanation of cleaning procedures; Removal of dirt with cleaning solutions) A container containing a cleaning liquid was set on the trajectory of the movable range of the discharge nozzle 2. A sodium hypochlorite aqueous solution (effective chlorine concentration 5%) was used as the cleaning liquid. Next, under the control of the control unit 100, the cleaning liquid was sucked up from the discharge nozzle 2 and discharged into the dilution tank 1. In addition, the control unit 100 sent an electrical signal to the three-way solenoid valve 10 for switching the cleaning bypass line, so that the cleaning liquid passes through the cleaning bypass line 13 side, and the liquid in the flow path is sucked up by the syringe pump 20, so that the cleaning liquid in the dilution tank 1 flows in the direction of the cleaning bypass line 13.

[0048] The control unit 100 repeats the discharge of the cleaning solution into the dilution tank 1 and the suction of the syringe pump 20, and when the cleaning solution fills the dilution tank 1 from the outlet of the cleaning bypass line 13 (i.e., the connection part 15 with the three-way solenoid valve 10 for switching the cleaning bypass line) to the upper edge of the dilution tank 1, stops the operation and allows the dilution tank 1 to stand for 6 minutes.

[0049] Next, the control unit 100 switches the three-way solenoid valve 17 for waste liquid discharge on the waste liquid line 16, while repeatedly discharging the cleaning liquid into the dilution tank 1 and suctioning with the syringe pump 20, and when the liquid is filled from the waste liquid outlet and the syringe pump 20 to the contact point between the diluted sample outlet flow path 5 and the dilution tank 1, the control unit 100 stops the operation and leaves it to stand for 7 minutes. After leaving it to stand, the control unit 100 switches the three-way solenoid valve 17 for waste liquid discharge, while sending liquid with the syringe pump 20, and collects the used cleaning liquid in a waste liquid container.

[0050] (Explanation of cleaning procedure; flushing out cleaning fluid from the cleaning bypass line) Since residual cleaning fluid can adversely affect the analysis of biological samples, the inner surface of the channel after cleaning must be rinsed with a diluent. The automatic processing performed by the control unit 100 or manual operations are as follows. A phosphate buffer solution was used as the diluent.

[0051] First, the control unit 100 discharges the diluent from the diluent outlet 3 into the dilution tank 1, then the control unit 100 discharges the diluent into the dilution tank 1 while switching the three-way solenoid valve 17 for waste liquid discharge operation, and when the dilution tank 1 is filled up to the upper edge, the syringe pump 20 sucks and delivers the liquid, recovers the remaining cleaning liquid and diluent in a waste liquid container, and washes the inner surface of the flow path with the diluent. The control unit 100 repeats this process 10 times.

[0052] (Explanation of cleaning procedure; rinsing off cleaning solution) The above-mentioned washing cannot wash away the portion from the branch point 6 to the dilution tank outlet 7 in the dilution tank 1. It is necessary to completely wash away even the slightest components of the cleaning liquid that have entered the portion from the branch point 6 to the dilution tank outlet 7 during washing. The automatic processing by the control unit 100 or the manual operation is as follows.

[0053] The control unit 100 switches the three-way solenoid valve 10 for switching the washing bypass line so that the liquid flows to the sensor side. Next, the diluent is discharged from the diluent outlet 3 into the dilution tank 1, and when the dilution tank 1 is filled up to the upper edge, the three-way solenoid valve 17 for waste liquid discharge operation is switched while the syringe pump 20 sucks and delivers the liquid, recovers the remaining washing liquid and diluent in a waste liquid container, and washes the area from the branch point 6 to the dilution tank outlet 7 with the diluent. The control unit 100 repeats this four times.

[0054] In the first embodiment of the present invention, it was possible to wash away biological dirt with a simple operation without replacing the sensor and the washing block, and the washing effect was equivalent to that when the washing block was used.

[0055] (Embodiment 2) The second embodiment is the same as the first embodiment, except that the settings for the cleaning and washing-off operations are input in advance to the control unit 100. In the second embodiment, the control unit 100 is set to perform the series of operations shown in the first embodiment at a predetermined date and time, for example, 18:00 on a Friday of the weekend.

[0056] In the second embodiment of the present invention, cleaning can be performed automatically at a set time without the user having to give instructions each time.

[0057] (Embodiment 3) The same as in the second embodiment except that the operations of cleaning and washing away the cleaning solution and the judgment of the index related to the quality of the measurement are set and inputted to the control unit 100 in advance. Here, the number of measurements is used as the index related to the quality of the measurement. The control unit 100 obtains information on the number of measurements from the analysis status at a predetermined date and time, for example, from 18:30 on Friday of the first week to 18:00 on Friday of the second week (the following week), and is set to perform a series of operations similar to those in the second embodiment at 18:00 on Friday of the second week if the average number of measurements per day exceeds 100.

[0058] In the third embodiment of the present invention, cleaning can be performed at an appropriate timing according to the usage status of the biological sample analyzer. Note that, although the number of measurements is used here as an index of quality, it is also possible to use the variance in values ​​and noise generation status when analyzing and calibrating biological samples, the pressure in the flow path, and the status of suspended matter and adhesions, etc. as indexes. [Industrial Applicability]

[0059] The present invention is suitable for use in an apparatus for analyzing biological samples such as urine, serum, plasma, whole blood, and cerebrospinal fluid. [Explanation of symbols]

[0060] 1 Dilution tank 2. Discharge nozzle for injecting biological samples or cleaning solutions into the dilution section 3 Dilution fluid outlet 4 Standard solution outlet 5. Dilution sample outlet flow path 6. Branching Point 7 Dilution tank outlet 8 Flow-through sensor 9 Flow-through sensor outlet 10. Three-way solenoid valve for switching the washing bypass line 13 Washing bypass line 14 Washing bypass line inlet 15 Washing bypass line outlet 16 Waste liquid line 17 Three-way solenoid valve for waste liquid discharge operation 19 Waste liquid section 20 Syringe Pump 21 Cleaning Solution 30 Cleaning Block 101 CPU (control unit) 102 ROM 103 RAM 104 Display 105 Network I / F

Claims

1. A dilution unit for diluting a biological sample; a discharge nozzle for injecting the biological sample or the cleaning solution into the dilution section; a flow-through sensor for analyzing the biological sample after dilution; A waste liquid section for disposing of liquid after use in analysis, A biological sample analyzer comprising: a washing solution bypass line branching off from said dilution section; said washing solution bypass line being connected via a valve to said waste solution section located downstream of said sensor.

2. 2. The biological sample analyzer according to claim 1, wherein the flow-through sensor for analyzing the diluted biological sample is an ion-selective electrode.

3. A control unit controls each part of the device including the valve, 3. The biological sample analyzer according to claim 1, wherein the control unit controls the opening and closing of the valve at a predetermined date and time, and automatically performs a cleaning operation.

4. 4. The biological sample analyzer according to claim 3, wherein the control unit automatically executes a cleaning operation when an index related to the quality of measurement detected by the sensor deviates from a threshold value.

Images